The Animal CORE will support all of the research projects in the program by providing the necessary genetically modified mice. One mission of the animal CORE will be to maintain mice for long-term studies to evaluate predisposition to cancer. A second mission of the animal CORE will be maintaining stocks of the genetically modified strains (e.g., Cdk4-R24C mutant, cdk4 null mutant, p107 knockout, pl30 knockout, p21 knockout), and to breed these strains together to produce fetuses of double and triple mutant homozygous genotypes. These fetuses will be used as a source of embryonic fibroblasts by the projects. Because fetuses with the desired double or triple mutant genotypes will constitute only a small fraction of the progeny, producing these fetuses to provide a continuous supply in support of the research projects will require a large amount of breeding, coupled with genotype analysis to identify the appropriate individuals. Mice will be housed and produced under barrier conditions that ensure continuing specific pathogen-free status. Centralization of the production and care of these mice under the animal CORE will limit the number of individuals handling the animals, thereby further safeguarding their health. Moreover, by centralizing the production and dispensation of these genetically valuable animals, the animal CORE will be able to coordinate usage among the different projects, avoid wastage, and achieve an economy of scale that will permit these studies to be completed at less expense than if undertaken separately.